PT - JOURNAL ARTICLE
AU - Fritz-Laylin, Lillian K.
AU - Lord, Samuel J.
AU - Mullins, R. Dyche
TI - Chytrid fungi construct actin-rich pseudopods, implicating actin regulators WASP and SCAR in an ancient mode of cell motility
DP - 2016 Jan 01
TA - bioRxiv
4099 - http://biorxiv.org/content/early/2016/05/04/051821.short
4100 - http://biorxiv.org/content/early/2016/05/04/051821.full
AB - Various cells scattered throughout the eukaryotic tree crawl across surfaces or through three-dimensional environments. Evidence now indicates that cell crawling is not a single behavior, but rather a collection of processes, driven by different molecular mechanisms. Understanding these mechanisms and their evolutionary relationships first requires narrowly defining mechanical modes of locomotion, and then identifying phenotypic and molecular markers of each. Here, we focus on a widely dispersed form of cell crawling characterized by dynamic, actin-filled pseudopods and weak, nonspecific adhesion to external substrates, a mode we refer to as "α-motility." Finding α-motility in cells ranging from free-living amoebae to immune cells hints at a single evolutionary origin of this complex process. By mining recently published genomic data, we identified a clear trend: only organisms with both WASP and SCAR/WAVE---two activators of branched actin assembly---make dynamic, three-dimensional pseudopods. While SCAR has been shown in some organisms to be an important driver of pseudopod formation, a role for WASP in this process is less clear. We hypothesize that these genes together represent a genetic signature of α-motility, and both proteins are used for pseudopod formation. We test our hypothesis by depleting WASP from human neutrophils, and confirm that both proteins are needed for explosive actin polymerization, pseudopod formation, and rapid cell migration. We also found that WASP and SCAR colocalize to the same dynamic signaling structures in living cells. Moreover, genomic retention of WASP together with SCAR also correctly predicts the presence of pseudopods in the disease-causing fungus Batrachochytrium dendrobatidis, making it the first fungus reported to undergo α-motility. By narrowing our focus to a single mode of cell migration while expanding our phylogenetic analysis to a variety of eukaryotes, we identified WASP together with SCAR as a conserved genetic marker of fast, low-adhesion cell crawling. Our cell-biology experiments argue that this conservation reflects their collaboration in the explosive actin assembly required to build dynamic pseudopods. These results represent the clearest evidence for a widely distributed mode of cell crawling with a single evolutionary origin.